Investigating the Possible Interfering Effect of COX-2 Inhibitors on Antimalarial Activity of Mefloquine and Artesunate

Main Article Content

Wanna Chaijaroenkul
Jirawadee Tippayapornswan
Maethee Vichitnontakarn
Kesara Na-Bangchang

Abstract

Cyclooxygenase (COX) is the key enzyme responsible for the production of prostanoids.  It plays important roles in the inflammatory process and pathogenesis of several diseases, including malaria. However, there has been no information of the inhibitory effects of COX inhibitors on inflammatory mediators and standard antimalarial drugs. Therefore, in this study, both selective and non-selective COX-2 inhibitors (aspirin, ibuprofen, piroxicam, and naproxen), alone or in combination, were investigated for their antimalarial activities in vitro. The antimalarial activity was assessed using the SYBR Green I fluorescent-based technique. For mefloquine- aspirin combination, the test wells consisted of mefloquine and aspirin at the ratios of 200:0, 140:30000, 100:50000, 60:70000, and 0:100000 nM. The concentration ratios for artesunate-aspirin were 50:0, 35:30000, 25:50000, 15:70000, and 0:100000 nM. The median (range) concentrations that inhibited parasite growth by 50% (IC50) of aspirin for K1 and 3D7 clones were 1,889 (1,600-2,792) and 2,417 (912-2,630) nM, respectively. The corresponding values of mefloquine were 10.1 (8.1-13.9) and 23.4 (22.9-24.7) nM, respectively. The corresponding values of artesunate were 2.5 (1.6-3.4) vs. 2.2 (1.2-3.2) nM, respectively. The corresponding values for mefloquine were 10 (8-14) and 23 (23-25) nM, respectively. The corresponding values for artesunate were 2.5 (2-3) vs. 2 (1-3) nM, respectively. The IC50 values of ibuprofen, piroxicam and naproxen were higher than 100,000 nM for both clones. The median (range) sum fractional inhibitory concentrations (FIC) of mefloquine-aspirin interaction for K1 and 3D7 P. falciparum clones were 0.82 (0.79-1.0) and 0.97 (0.83-1.1), respectively. The corresponding sum FICs of artesunate-aspirin were 0.94 (0.88-0.95) and 0.95 (0.92-0.97), respectively. Results indicate indifferent antimalarial interaction between these two drugs when used in combination. 

Downloads

Download data is not yet available.

Article Details

How to Cite
Chaijaroenkul, W., Tippayapornswan, J. ., Vichitnontakarn, M. ., & Na-Bangchang, K. (2021). Investigating the Possible Interfering Effect of COX-2 Inhibitors on Antimalarial Activity of Mefloquine and Artesunate. Journal of Basic and Applied Pharmacology, 43(1), 14–20. Retrieved from https://li01.tci-thaijo.org/index.php/JBAP/article/view/248590
Section
Research Articles
Author Biography

Wanna Chaijaroenkul, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Pathumthani, Thailand

Research Publications

  1. Thongdee P, Chaijaroenkul W, Kuesap J, Na-Bangchang K. Nested-PCR and a new ELISA-based NovaLisa test kit for malaria diagnosis in an endemic area of Thailand. Korean J Parasitol. 2014 Aug;52(4):377-81.
  2. Sumsakul W, Plengsuriyakarn T, Chaijaroenkul W, Viyanant V, Karbwang J, Na-Bangchang K. Antimalarial activity of plumbagin in vitro and in animal models. BMC Complement Altern Med. 2014;14(1):15.
  3. Phompradit P, Muhamad P, Wisedpanichkij R, Chaijaroenkul W, Na-Bangchang K. Four years' monitoring of in vitro sensitivity and candidate molecular markers of resistance of Plasmodium falciparum to artesunate-mefloquine combination in the Thai-Myanmar border. Malar J. 2014;13(1):23.
  4. Phompradit P, Muhamad P, Chaijaroenkul W, Na-Bangchang K. Genetic polymorphisms of candidate markers and in vitro susceptibility of Plasmodium falciparum isolates from Thai-Myanmar border in relation to clinical response to artesunate-mefloquine combination. Acta Trop. 2014 Jul 5;139C:77-83.
  5. Kuesap J, Chaijaroenkul W, Ketprathum K, Tattiyapong P, Na-Bangchang K. Evolution of genetic polymorphisms of Plasmodium falciparum merozoite surface protein (PfMSP) in Thailand. Korean J Parasitol. 2014 Feb;52(1):105-9.
  6. Chaijaroenkul W, Thiengsusuk A, Rungsihirunrat K, Ward SA, Na-Bangchang K. Proteomics analysis of antimalarial targets of Garcinia mangostana Linn. Asian Pac J Trop Biomed. 2014 Jul;4(7):515-9.
  7. Chaijaroenkul W, Mubaraki M, Ward SA, Na-Bangchang K. Metabolite footprinting of Plasmodium falciparum following exposure to Garcinia mangostana Linn. crude extract. Exp Parasitol. 2014 Aug 4.
  8. Bunyong R, Chaijaroenkul W, Plengsuriyakarn T, Na-Bangchang K. Antimalarial activity and toxicity of Garcinia mangostana Linn. Asian Pac J Trop Med. 2014 Sep;7(9):693-8.
  9. Thiengsusuk A, Chaijaroenkul W, Na-Bangchang K. Antimalarial activities of medicinal plants and herbal formulations used in Thai traditional medicine. Parasitol Res. 2013 Apr;112(4):1475-81.
  10. Rungsihirunrat K, Kuesap J, Chaijaroenkul W, Na Bangchang K. Distribution and Emergence of Chloroquine-Resistant Plasmodium Vivax. J Health Res. 2013;27(1):57-65.
  11. Na-Bangchang K, Muhamad P, Ruaengweerayut R, Chaijaroenkul W, Karbwang J. Identification of resistance of Plasmodium falciparum to artesunate-mefloquine combination in an area along the Thai-Myanmar border: integration of clinico-parasitological response, systemic drug exposure, and in vitro parasite sensitivity. Malar J. 2013;12:263.
  12. Muhamad P, Chaijaroenkul W, Phompradit P, Rueangweerayut R, Tippawangkosol P, Na-Bangchang K. Polymorphic patterns of pfcrt and pfmdr1 in Plasmodium falciparum isolates along the Thai-Myanmar border. Asian Pac J Trop Biomed. 2013 Dec;3(12):931-5.
  13. Rungsihirunrat K, Chaijaroenkul W, Siripoon N, Seugorn A, Thaithong S, Na-Bangchang K. Comparison of protein patterns between Plasmodium falciparum mutant clone T9/94-M1-1(b3) induced by pyrimethamine and the original parent clone T9/94. Asian Pacific Journal of Tropical Biomedicine. 2012;2(1):66-9.
  14. Plengsuriyakarn T, Viyanant V, Eursitthichai V, Tesana S, Chaijaroenkul W, Itharat A, et al. Cytotoxicity, toxicity, and anticancer activity of Zingiber officinale Roscoe against cholangiocarcinoma. Asian Pac J Cancer Prev. 2012;13(9):4597-606.
  15. Pacharapruethipakorn N, Chaijaroenkul W, Na Bangchang K, Itharat A, Aunpad R. Screenings Test of Traditional Medicinal Herbs for Bactericidal Activity and Their Effects Determination. J Health Res. 2012;26.
  16. Wisedpanichkij R, Grams R, Chaijaroenkul W, Na-Bangchang K. Confutation of the existence of sequence-conserved cytochrome P450 enzymes in Plasmodium falciparum. Acta Trop. 2011 Jul;119(1):19-22.
  17. Sriwanitchrak P, Viyanant V, Chaijaroenkul W, Srivatanakul P, Gram HR, Eursiddhichai V, et al. Proteomics analysis and evaluation of biomarkers for detection of cholangiocarcinoma. Asian Pac J Cancer Prev. 2011;12(6):1503-10.
  18. Rungsihirunrat K, Chaijaroenkul W, Siripoon N, Seugorn A, Na-Bangchang K. Genotyping of polymorphic marker (MSP3alpha and MSP3beta) genes of Plasmodium vivax field isolates from malaria endemic of Thailand. Trop Med Int Health. 2011 Mar 29;16(7):794-801.
  19. Phompradit P, Wisedpanichkij R, Muhamad P, Chaijaroenkul W, Na-Bangchang K. Molecular analysis of pfatp6 and pfmdr1 polymorphisms and their association with in vitro sensitivity in Plasmodium falciparum isolates from the Thai-Myanmar border. Acta Trop. 2011 Oct-Nov;120(1-2):130-5.
  20. Phompradit P, Kuesap J, Chaijaroenkul W, Rueangweerayut R, Hongkaew Y, Yamnuan R, et al. Prevalence and distribution of glucose-6-phosphate dehydrogenase (G6PD) variants in Thai and Burmese populations in malaria endemic areas of Thailand. Malar J. 2011 Dec 15;10(1):368.
  21. Muhamad P, Ruengweerayut R, Chacharoenkul W, Rungsihirunrat K, Na-Bangchang K. Monitoring of clinical efficacy and in vitro sensitivity of Plasmodium vivax to chloroquine in area along Thai Myanmar border during 2009-2010. Malar J. 2011;10(1):44.
  22. Muhamad P, Phompradit P, Sornjai W, Maensathian T, Chaijaroenkul W, Rueangweerayut R, et al. Polymorphisms of Molecular Markers of Antimalarial Drug Resistance and Relationship with Artesunate-Mefloquine Combination Therapy in Patients with Uncomplicated Plasmodium falciparum Malaria in Thailand. Am J Trop Med Hyg. 2011 Sep;85(3):568-72.
  23. Muhamad P, Chaijaroenkul W, Congpuong K, Na-Bangchang K. SYBR Green I and TaqMan quantitative real-time polymerase chain reaction methods for the determination of amplification of Plasmodium falciparum multidrug resistance-1 gene (pfmdr1). J Parasitol. 2011 Oct;97(5):939-42.
  24. Muhamad P, Chaijareonkul W, Rungsihirunrat K, Ruengweerayut R, Na Bangchang K. Assessment of in vitro sensitivity of Plasmodium vivax fresh isolates. Asian Pacific Journal of Tropical Biomedicine. 2011:49-53.
  25. Chaijaroenkul W, Wongchai T, Ruangweerayut R, Na-Bangchang K. Evaluation of Rapid Diagnostics for Plasmodium falciparum and P. vivax in Mae Sot Malaria Endemic Area, Thailand. Korean J Parasitol. 2011 Mar;49(1):33-8.
  26. Chaijaroenkul W, Ward SA, Mungthin M, Johnson D, Owen A, Bray PG, et al. Sequence and gene expression of chloroquine resistance transporter (pfcrt) in the association of in vitro drugs resistance of Plasmodium falciparum. Malar J. 2011;10(1):42.
  27. Chaijaroenkul W, Viyanant V, Mahavorasirikul W, Na-Bangchang K. Cytotoxic Activity of Artemisinin Derivatives Against Cholangiocarcinoma (CL-6) and Hepatocarcinoma (Hep-G2) Cell Lines. Asian Pac J Cancer Prev. 2011;12(1):55-9.
  28. Chaijaroenkul W, Rungsihirunrat K, Na-Bangchang K. Metabolomics approaches in parasitology. J Health Res. 2011;25(1):25-33.
  29. Wisedpanichkij R, Chaijareonkul W, Muhamad P, Prompradit P, Na Bangchang K. Polymorphisms of the oxidant enzymes glutathione S-transferase and glutathione reductase and their association with resistance of Plasmodium falciparum isolates to antimalarial drugs. Asian Pacific J Trop Med. 2010;3(9):673-7.
  30. Wisedpanichkij R, Chaijareonkul W, Muhamad P, Na Bangchang K. Investigation of the association between prostaglandin D2 (PGD2) levels and malaria pathogenicity and severity J Health Res. 2010;26(4):143-9.
  31. Na-Bangchang K, Ruengweerayut R, Mahamad P, Ruengweerayut K, Chaijaroenkul W. Declining in efficacy of a three-day combination regimen of mefloquine-artesunate in a multi-drug resistance area along the Thai-Myanmar border. Malar J. 2010;9:273.
  32. Mungthin M, Suwandittakul N, Chaijaroenkul W, Rungsrihirunrat K, Harnyuttanakorn P, Seugorn A, et al. The patterns of mutation and amplification of Plasmodium falciparum pfcrt and pfmdr1 genes in Thailand during the year 1988 to 2003. Parasitol Res. 2010 Aug;107(3):539-45.
  33. Mahavorasirikul W, Viyanant V, Chaijaroenkul W, Itharat A, Na-Bangchang K. Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells in vitro. BMC Complement Altern Med. 2010;10:55.
  34. Chaijaroenkul W, Wisedpanichkij R, Na-Bangchang K. Monitoring of in vitro susceptibilities and molecular markers of resistance of Plasmodium falciparum isolates from Thai-Myanmar border to chloroquine, quinine, mefloquine and artesunate. Acta Trop. 2010 Feb;113(2):190-4.
  35. Wisedpanichkij R, Chaijaroenkul W, Sangsuwan P, Tantisawat J, Boonprasert K, Na-Bangchang K. In vitro antimalarial interactions between mefloquine and cytochrome P450 inhibitors. Acta Trop. 2009 Oct;112(1):12-5.
  36. Suwandittakul N, Chaijaroenkul W, Harnyuttanakorn P, Mungthin M, Na Bangchang K. Drug resistance and in vitro susceptibility of Plasmodium falciparum in Thailand during 1988-2003. Korean J Parasitol. 2009 Jun;47(2):139-44.
  37. Rungsihirunrat K, Chaijaroenkul W, Seugorn A, Na-Bangchang K, Thaithong S. Association between chloroquine resistance phenotypes and point mutations in pfcrt and pfmdr1 in Plasmodium falciparum isolates from Thailand. Acta Trop. 2009 Jan;109(1):37-40.
  38. Aunpad R, Somsri S, Na-Bangchang K, Udomsangpetch R, Mungthin M, Adisakwattana P, et al. The effect of mimicking febrile temperature and drug stress on malarial development. Ann Clin Microbiol Antimicrob. 2009;8:19.
  39. Chaijaroenkul W, Pruktal P, Muhamad P, Na-Bangchang K. Assessment of in vitro antimalarial interactions between dihydroartemisinin and fosmidomycin. Southeast Asian J Trop Med Public Health. 2007 Sep;38(5):791-5.
  40. Chaijaroenkul W, Tippawangkosol P, Kuesap J, Congpuong K, Ruenweerayut R, Suwandittakul N, et al. Comparison of two in vitro sensitivity tests for Plasmodium falciparum. Southeast Asian J Trop Med Public Health. 2006 Jan;37(1):5-12.
  41. Chaijaroenkul W, Bangchang KN, Mungthin M, Ward SA. In vitro antimalarial drug susceptibility in Thai border areas from 1998-2003. Malar J. 2005;4:37.

References

Anggard E, Matschinsky FM, Samuelsson B. Prostaglandins: enzymatic analysis. Science. 1969 Jan 31;163(3866):479-80.

Dinarello CA, Wolff SM. Pathogenesis of fever in man. N Engl J Med. 1978 Mar16;298(11):607-12.

Goodwin JS, Ceuppens J. Regulation of the immune response by prostaglandins. J Clin Immunol. 1983 Oct;3(4):295-315.

Kilunga KB, Eguchi N, Urade Y, Yamashita K, Mitamura T, Tai K, et al. Plasmodium falciparum produces prostaglandins that are pyrogenic, somno-genic, and immunosuppressive substances in humans. J Exp Med. 1998 Sep 21;188(6):1197-202.

Trager W, Jensen JB. Human malaria parasites in continuous culture. Science. 1976 Aug 20;193(4254):673-5.

Bennett TN, Paguio M, Gligorijevic B, Seudieu C, Kosar AD, Davidson E, et al. Novel, rapid, and inexpensive cell-based quantification of antimalarial drug efficacy. Antimicrob Agents Chemother. 2004 May;48(5):1807-10.

Smilkstein M, Sriwilaijaroen N, Kelly JX, Wilairat P, Riscoe M. Simple and inexpensive fluorescence-based technique for high-throughput antimalarial drug screening. Antimicrob Agents Chemother. 2004 May;48(5):1803-6.

Fivelman QL, Adagu IS, Warhurst DC. Modified fixed-ratio isobologram method for studying in vitro interactions between atovaquone and proguanil or dihydro-artemisinin against drug-resistant strains of Plasmodium falciparum. Antimicrob Agents Chemother. 2004 Nov;48(11):4097-102.

Gupta S, Thapar MM, Wernsdorfer WH, Björkman A. In vitro interactions of artemisinin with atovaquone, quinine, and mefloquine against Plasmodium falciparum. Antimicrob Agents Chemother. 2002; 46:1510-5.

Schwarzer E, Kuhn H, Valente E, Arese P. Malaria-parasitized erythrocytes and hemozoin nonenzymatically generate large amounts of hydroxy fatty acids that inhibit monocyte functions. Blood. 2003 Jan 15;101(2):722-8.

Anyona SB, Hengartner NW, Raballah E, Ong'echa JM, Lauve N, Cheng Q, et al. Cyclooxygenase-2 haplotypes influence the longitudinal risk of malaria and severe malarial anemia in Kenyan children from a holoendemic transmission region. J Hum Genet. 2020 Jan;65(2):99-113.

Anyona SB, Kempaiah P, Raballah E, Davenport GC, Were T, Konah SN, et al. Reduced systemic bicyclo-prostaglandin-E2 and cyclooxygenase-2 gene expression are associated with inefficient erythropoiesis and enhanced uptake of monocytic hemozoin in children with severe malarial anemia. Am J Hematol. 2012 Aug; 87(8):782-9.

Kuesap J, Na-Bangchang K. Possible role of heme oxygenase-1 and prosta-glandins in the pathogenesis of cerebral malaria: heme oxygenase-1 induction by prostaglandin D2 and metabolite by a human astrocyte cell line. Korean J Parasitol. 2010 Mar;48(1):15-21.

Keller CC, Davenport GC, Dickman KR, Hittner JB, Kaplan SS, Weinberg JB, et al. Suppression of prostaglandin E2 by malaria parasite products and anti-pyretics promotes overproduction of tumor necrosis factor-α: association with the pathogenesis of childhood malarial anemia. J Infect Dis. 2006 May 15; 193(10):1384-93.

Perkins DJ, Hittner JB, Mwaikambo ED, Granger DL, Weinberg JB, Anstey NM. Impaired systemic production of prostaglandin E2 in children with cerebral malaria. J Infect Dis. 2005 May 1;191(9):1548-57.

Kunkel SL, Spengler M, May MA, Spengler R, Larrick J, Remick D. Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J Biol Chem. 1988 Apr 15;263(11):5380-4.

Renz H, Gong JH, Schmidt A, Nain M, Gemsa D. Release of tumor necrosis factor-alpha from macrophages. Enhancement and suppression are dose-dependently regulated by prostaglandin E2 and cyclic nucleotides. J Immunol. 1988 Oct 1;141(7):2388-93.

Most read articles by the same author(s)

1 2 3 > >>